Ipilimumab With or Without Talimogene Laherparepvec in Unresected Melanoma
NCT ID: NCT01740297
Last Updated: 2024-05-14
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
217 participants
INTERVENTIONAL
2013-02-07
2021-03-09
Brief Summary
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Detailed Description
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The phase 2 part of the study is an open-label, multicenter, randomized study to further assess the safety and to evaluate the efficacy of talimogene laherparepvec in combination with ipilimumab. Participants will be randomized 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab alone.
Participants randomized before amendment 2 will be stratified by stage of disease (stage IIIB/C, IVM1a, and stage IVM1b vs IVM1c) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E (a mutation resulting in a substitution of glutamic acid for valine at codon 600) (mutation vs mutation not present). Participants randomized after amendment 2 will be stratified by stage of disease (stage IIIB/C and IVM1a vs stage IVM1b and IVM1c) and prior therapy (treatment naïve vs previously treated with systemic anticancer immunotherapy vs previously treated with systemic anticancer treatment other than immunotherapy).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
Phase 2 was an open-label multicenter, randomized design to further assess safety and to evaluate efficacy of talimogene laherparepvec in combination with ipilimumab.
TREATMENT
NONE
Study Groups
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Phase 1b: Talimogene Laherparepvec + Ipilimumab
Participants received talimogene laherparepvec at an initial dose of 10⁶ plaque-forming units (PFU)/mL injected into 1 or more skin, nodal, or subcutaneous tumors. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until complete response (CR), all injectable tumors had disappeared, confirmed disease progression per the modified immune-related response criteria (irRC), or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab administered intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6).
Talimogene laherparepvec
Talimogene laherparepvec administered by intratumoral injection on Day 1 of Week 1, Day 1 of Week 4, then every two weeks thereafter.
Ipilimumab
Ipilimumab administered intravenously every 3 weeks for a total of 4 infusions.
Phase 2: Ipilimumab
Participants received ipilimumab 3 mg/kg intravenously every 3 weeks for a total of 4 infusions starting at week 1.
Ipilimumab
Ipilimumab administered intravenously every 3 weeks for a total of 4 infusions.
Phase 2: Talimogene Laherparepvec + Ipilimumab
Participants received talimogene laherparepvec at an initial dose of 10⁶ PFU/mL injected into 1 or more skin, nodal, or subcutaneous tumors. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until CR, all injectable tumors had disappeared, confirmed disease progression per the modified irRC, or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6).
Talimogene laherparepvec
Talimogene laherparepvec administered by intratumoral injection on Day 1 of Week 1, Day 1 of Week 4, then every two weeks thereafter.
Ipilimumab
Ipilimumab administered intravenously every 3 weeks for a total of 4 infusions.
Interventions
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Talimogene laherparepvec
Talimogene laherparepvec administered by intratumoral injection on Day 1 of Week 1, Day 1 of Week 4, then every two weeks thereafter.
Ipilimumab
Ipilimumab administered intravenously every 3 weeks for a total of 4 infusions.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c disease that is not suitable for surgical resection
* Phase1: Treatment naïve: Must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy for unresected stage IIIB to IV melanoma.
* Phase 2:
* Either treatment naïve or received only one line of systemic anticancer therapy if v-raf murine sarcoma viral oncogene homolog B1 (BRAF) wild-type or up to two lines of systemic anticancer therapy including one BRAF inhibitor-containing regimen if BRAF mutant. Treatments given in an adjuvant setting (eg, interferon, radiotherapy, isolated limb perfusion, or investigational agents) are not considered as prior lines of therapy. No prior talimogene laherparepvec, other oncolytic virus therapies, or tumor vaccines are allowed, even if given in the adjuvant setting.
* Subjects treated with prior ipilimumab must have had partial response (PR), complete response (CR), or at least 6 months of stable disease followed by disease progression.
* Subjects previously treated with anti-program death-1 (PD1) or anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) antibodies must not have discontinued therapy due to any treatment-related adverse events including immune-related adverse events. Prior treatment-related adverse events should also be fully resolved and not requiring treatment for at least 28 days prior to randomization.
* Measurable disease defined as one or both of the following
* at least 1 melanoma lesion that can be accurately and serially measured in at least 2 dimensions and for which the longest diameter is ≥ 10 mm and with perpendicular diameter ≥ 5 mm as measured by contrast-enhanced or spiral computed tomography (CT) scan for visceral or nodal/soft tissue disease. Lymph nodes must measure \> 15 mm in their short axis to be considered measurable by CT scan.
* at least 1 superficial cutaneous or subcutaneous melanoma lesion that can be accurately and serially measured in at least 2 dimensions and for which the short axis is ≥ 5 mm as measured by calipers
* Injectable disease (ie, suitable for direct injection or through the use of ultrasound \[US\] guidance) defined as follows:
* at least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion ≥ 5 mm in longest diameter
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Adequate hematologic, hepatic, renal, and coagulation functions
Exclusion Criteria
* History or evidence of melanoma associated with immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia)
* Phase 1b: History or evidence of central nervous system (CNS) metastases
* Phase 2: Clinically active cerebral melanoma metastases. Subjects with up to 3 cerebral metastases, and neurological performance status of 0 may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, or Gamma knife therapy, with no evidence of progression, and have not required steroids, for at least 2 months prior to enrollment.
* History or evidence of symptomatic autoimmune disease (such as pneumonitis, glomerulonephritis, vasculitis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, scleroderma, or other), or history of autoimmune disease that required systemic treatment (ie, use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past 2 months prior to enrollment. Replacement therapy (eg, thyroxine for hypothyroidism, insulin for diabetes mellitus) is not considered a form of systemic treatment for autoimmune disease.
* History of or plan for splenectomy or splenic irradiation
* Active herpetic skin lesions or prior complications of herpes simplex type-1 virus (HSV-1) infection (eg, herpetic keratitis or encephalitis).
* Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use
* Known human immunodeficiency virus (HIV) disease
* Known acute or chronic hepatitis B or hepatitis C infection
* Phase 1b: Prior talimogene laherparepvec, ipilimumab, other CTLA-4 inhibitors, PD-1 inhibitors, or tumor vaccine
* Phase 2: Prior talimogene laherparepvec, other oncolytic virus therapies, or tumor vaccines
* Currently receiving or less than 28 days since ending systemic anticancer treatment for unresected stage IIIB to IV melanoma
18 Years
ALL
No
Sponsors
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Amgen
INDUSTRY
Responsible Party
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Principal Investigators
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MD
Role: STUDY_DIRECTOR
Amgen
Locations
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Research Site
Tucson, Arizona, United States
Research Site
Beverly Hills, California, United States
Research Site
Los Angeles, California, United States
Research Site
Los Angeles, California, United States
Research Site
Los Angeles, California, United States
Research Site
San Francisco, California, United States
Research Site
Santa Rosa, California, United States
Research Site
Aurora, Colorado, United States
Research Site
Jacksonville, Florida, United States
Research Site
Jacksonville, Florida, United States
Research Site
Lakeland, Florida, United States
Research Site
Miami, Florida, United States
Research Site
Chicago, Illinois, United States
Research Site
Indianapolis, Indiana, United States
Research Site
Indianapolis, Indiana, United States
Research Site
Iowa City, Iowa, United States
Research Site
Louisville, Kentucky, United States
Research Site
Minneapolis, Minnesota, United States
Research Site
St Louis, Missouri, United States
Research Site
Morristown, New Jersey, United States
Research Site
New Brunswick, New Jersey, United States
Research Site
New York, New York, United States
Research Site
New York, New York, United States
Research Site
Chapel Hill, North Carolina, United States
Research Site
Canton, Ohio, United States
Research Site
Cincinnati, Ohio, United States
Research Site
Charleston, South Carolina, United States
Research Site
Nashville, Tennessee, United States
Research Site
Houston, Texas, United States
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Salt Lake City, Utah, United States
Research Site
Richmond, Virginia, United States
Research Site
Milwaukee, Wisconsin, United States
Research Site
Bordeaux, , France
Research Site
Grenoble, , France
Research Site
Lille, , France
Research Site
Nantes, , France
Research Site
Paris, , France
Research Site
Göttingen, , Germany
Research Site
Kiel, , Germany
Research Site
Tübingen, , Germany
Countries
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References
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Chesney J, Puzanov I, Collichio F, Singh P, Milhem MM, Glaspy J, Hamid O, Ross M, Friedlander P, Garbe C, Logan TF, Hauschild A, Lebbe C, Chen L, Kim JJ, Gansert J, Andtbacka RHI, Kaufman HL. Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma. J Clin Oncol. 2018 Jun 10;36(17):1658-1667. doi: 10.1200/JCO.2017.73.7379. Epub 2017 Oct 5.
Puzanov I, Milhem MM, Minor D, Hamid O, Li A, Chen L, Chastain M, Gorski KS, Anderson A, Chou J, Kaufman HL, Andtbacka RH. Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma. J Clin Oncol. 2016 Aug 1;34(22):2619-26. doi: 10.1200/JCO.2016.67.1529. Epub 2016 Jun 13.
Chesney J, Puzanov I, Collichio F, Milhem MM, Hauschild A, Chen L, Sharma A, Garbe C, Singh P, Mehnert JM. Patterns of response with talimogene laherparepvec in combination with ipilimumab or ipilimumab alone in metastatic unresectable melanoma. Br J Cancer. 2019 Aug;121(5):417-420. doi: 10.1038/s41416-019-0530-6. Epub 2019 Jul 29.
Dummer R, Hoeller C, Gruter IP, Michielin O. Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors. Cancer Immunol Immunother. 2017 Jun;66(6):683-695. doi: 10.1007/s00262-017-1967-1. Epub 2017 Feb 25.
Chesney JA, Puzanov I, Collichio FA, Singh P, Milhem MM, Glaspy J, Hamid O, Ross M, Friedlander P, Garbe C, Logan T, Hauschild A, Lebbe C, Joshi H, Snyder W, Mehnert JM. Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial. J Immunother Cancer. 2023 May;11(5):e006270. doi: 10.1136/jitc-2022-006270.
Related Links
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AmgenTrials clinical trials website
Other Identifiers
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2012-000307-32
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
20110264
Identifier Type: -
Identifier Source: org_study_id
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